crossing96/oncoscreening huggingface dataset:
Prognostic and clinicopathologic value of ki-67 and profilin 1 immunohistochemical expression in primary pT1 urothelial bladder cancer.	PURPOSE: To investigate the prognostic and clinicopathologic value of Ki-67 and profilin 1 immunohistochemical expression in primary pT1 papillary urothelial bladder cancer. MATERIALS AND METHODS: This study included 88 male and 13 female pT1 primary bladder cancer patients. Demographic characteristics, tumor histological grade, tumor number, presence of concomitant carcinoma in situ, tumor size, and status of recurrence or progression were recorded for each patient. Expression of Ki-67 and profilin 1 was evaluated by immunohistochemical analysis of paraffin-embedded tumor tissues. The Pearson's Chi-square test was used for the analysis of qualitative data, and the Kaplan-Meier method and the log-rank test were used for the survival analysis. RESULTS: In the mean follow-up period of 52 months, 52 (51.5%) patients experienced recurrence, 24 (23.8%) patients experienced progression, and 17 (16.8%) patients died from bladder cancer-related causes. Ki-67 expression was significantly associated with tumor histological grade (P = 0.001). In multivariate analysis, Ki-67 positivity had significantly worse outcome for recurrence (P = 0.006) and mortality (P = 0.022). Ki-67-positive (Ki-67 index ≥15%) patients had shorter recurrence-free (P = 0.003), progression-free (P = 0.002), and cancer-specific (P = 0.003) survival. However, no statistically significant relationship was found between profilin 1 expression and clinicopathologic features and prognosis. CONCLUSIONS: Ki-67 is a highly predictive biomarker for recurrence-free, progression-free, and cancer-specific survival in pT1 bladder cancer patients, in whom prediction of recurrence and progression are difficult. Ki-67 expression can be safely combined with other prognostic factors. However, in pT1 bladder cancer patients, no significant relationship was found between profilin 1 expression and tumor characteristics or prognostic parameters.	bladder
Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer.	OBJECTIVES: To examine the usefulness of the texture analysis (TA) of apparent diffusion coefficient (ADC) maps in predicting the chemoradiotherapy (CRT) response of muscle-invasive bladder cancer (MIBC). METHODS: We reviewed 45 MIBC patients who underwent cystectomy after CRT. CRT response was assessed through histologic evaluation of cystectomy specimens. Two radiologists determined the volume of interest for the index lesions on ADC maps of pretherapeutic 1.5-T MRI and performed TA using the LIFEx software. Forty-six texture features (TFs) were selected based on their contribution to the prediction of CRT sensitivity. To evaluate diagnostic performance, diagnostic models from the selected TFs were created using random forest (RF) and support vector machine (SVM), respectively. RESULTS: Twenty-three patients achieved pathologic complete response (pCR) to CRT. The feature selection identified first quartile ADC (Q1 ADC), gray-level co-occurrence matrix (GLCM) correlation, and GLCM homogeneity as important in predicting CRT response. Patients who achieved pCR showed significantly lower Q1 ADC and GLCM correlation values (0.66 × 10(-3) mm(2)/s and 0.53, respectively) than those who did not (0.81 × 10(-3) mm(2)/s and 0.70, respectively; p < 0.05 for both). The AUCs of the RF and SVM models incorporating the selected TFs were 0.82 (95% confidence interval [CI]: 0.67-0.97) and 0.96 (95% CI: 0.91-1.00), respectively, and the AUC of the SVM model was better than that of the mean ADC value (0.76, 95% CI: 0.61-0.90; p = 0.0037). CONCLUSION: TFs can serve as imaging biomarkers in MIBC patients for predicting CRT sensitivity. TAs of ADC maps can potentially optimize patient selection for CRT. KEY POINTS: • Texture analysis of ADC maps and feature selection identified important texture features for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The machine learning model incorporating the texture features set, which included first quartile ADC, GLCM correlation, and GLCM homogeneity, showed high performance in predicting chemoradiotherapy response. • Texture features could serve as imaging biomarkers that optimize eligible patient selection for chemoradiotherapy in muscle-invasive bladder cancer.	bladder
Evaluation of the Cancer of Bladder Risk Assessment (COBRA) Score in the Cancer Genome Atlas (TCGA) Bladder Cancer Cohort.	OBJECTIVE: To evaluate the Cancer of the Bladder Risk Assessment (COBRA) score in The Cancer Genome Atlas (TCGA) bladder cancer cohort. Second, to investigate the utility of the COBRA score within each bladder cancer molecular subtype following radical cystectomy (RC) and determine if it can help identify candidates for adjuvant therapies and clinical trials. METHODS: Among the TCGA bladder cancer cohort (n = 412), RC pathology reports were reviewed to calculate COBRA scores. Kaplan-Meier survival curves along with univariable and multivariable Cox proportional hazard models were used to determine the clinical utility of the COBRA score to predict overall survival (OS) within the overall cohort and within each molecular subtype (if n>30 within subtype). RESULTS: In the analytic cohort (n = 273) there was a median follow-up of 18 months. Higher COBRA score was associated with significant increased risk of death in both univariable (HR = 1.52 per point [PP] 95% CI [1.32, 1.75)] and multivariable models (HR = 1.54 PP 95% CI [1.32, 1.79]). This remained true in multivariable models stratified by molecular subtype for basal (HR = 1.37 PP 95% CI [1.07, 1.74]), luminal infiltrated (HR = 1.70 PP 95% CI [1.10, 2.64]), and luminal papillary (HR = 1.62 PP 95% CI [1.28, 2.06]) tumors. CONCLUSION: Our findings validate the COBRA score in the TCGA bladder cancer cohort. This suggests the COBRA score can be used in conjunction with molecular subtyping information to help guide clinical decision-making following RC to improve risk stratification and allow for earlier identification of candidates for adjuvant therapies and clinical trials.	bladder
Stratification of urothelial bladder carcinoma depending on immunohistochemical expression of GATA3 and CK5/6.	Bladder urothelial carcinoma (BUC) has two pathways with distinct molecular features and prognosis, non-muscle invasive (NMI) and muscle invasive (MI) tumors. The aim is to investigate the expression of GATA3 and CK5/6 in BUC with correlation to clinicopathologic parameters, including their impact on survival beside their potential use to stratify cases into prognostic subgroups. This study included 80 cases of BUC stained immunohistochemically by GATA3 and CK5/6. The cases were divided into four groups regarding expression status of both markers (luminal, basal, mixed, and null). GATA3 percentage of expression decreased in urothelial carcinoma with squamous differentiation, MI tumors, high-grade tumors, tumors with involved lymph nodes, presence of perineural invasion, presence of bilharziasis, presence of lympho-vascular invasion, and high mitotic count. CK5/6 positivity was higher in urothelial carcinoma cases with squamous differentiation, MI tumors, and presence of perineural invasion. Pure urothelial carcinoma and NMI were in favor of luminal group (GATA3 +ve/CK5/6 -ve). Univariate analysis showed that the presence of bilharziasis was associated with shorter PFS (p = .04). GATA3 and CK5/6 could be used for the stratification of urothelial bladder carcinoma into subtypes with different characteristics. Luminal bladder cancer represents the most common type (60%) that carries favorable features. Bilharziasis-associated urothelial carcinoma carries poor outcome manifested by short PFS.	bladder
Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in muscle-invasive bladder cancer.	Immunotherapy that block PD-1-PD-L1 pathway can induce durable tumor control and result in the long-term survival of patients with advanced bladder cancers. However, these responses only occur in a subset of patients. We study gene expression profiles in 1763 muscle-invasive bladder cancers (MIBCs) and 11,835 solid tumors from TCGA. We establish an immune-based classification on the basis of the composition of the tumor microenvironment and identify six distinct phenotypes. The class F was characterized by a strong tertiary lymphoid structures (TLSs) related gene expression signature. Pan-cancer gene expression analysis of tertiary lymphoid structure markers in 11,835 solid tumors from TCGA unveiled the heterogeneity of TLSs abundance both within and between human cancer types. The class F group demonstrated improved survival and a high response rate to PD1 blockade. This work confirms the immune subtypes in patients with MIBC, and unravels the potential of TLS signatures to guide clinical decision-making and treatments.	bladder
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex.	Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.	bladder
Machine Learning Methods to Identify Missed Cases of Bladder Cancer in Population-Based Registries.	PURPOSE: Population-based cancer incidence rates of bladder cancer may be underestimated. Accurate estimates are needed for understanding the burden of bladder cancer in the United States. We developed and evaluated the feasibility of a machine learning-based classifier to identify bladder cancer cases missed by cancer registries, and estimated the rate of bladder cancer cases potentially missed. METHODS: Data were from population-based cohort of 37,940 bladder cancer cases 65 years of age and older in the SEER cancer registries linked with Medicare claims (2007-2013). Cases with other urologic cancers, abdominal cancers, and unrelated cancers were included as control groups. A cohort of cancer-free controls was also selected using the Medicare 5% random sample. We used five supervised machine learning methods: classification and regression trees, random forest, logic regression, support vector machines, and logistic regression, for predicting bladder cancer. RESULTS: Registry linkages yielded 37,940 bladder cancer cases and 766,303 cancer-free controls. Using health insurance claims, classification and regression trees distinguished bladder cancer cases from noncancer controls with very high accuracy (95%). Bacille Calmette-Guerin, cystectomy, and mitomycin were the most important predictors for identifying bladder cancer. From 2007 to 2013, we estimated that up to 3,300 bladder cancer cases in the United States may have been missed by the SEER registries. This would result in an average of 3.5% increase in the reported incidence rate. CONCLUSION: SEER cancer registries may potentially miss bladder cancer cases during routine reporting. These missed cases can be identified leveraging Medicare claims and data analytics, leading to more accurate estimates of bladder cancer incidence.	bladder
Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors.	BACKGROUND: Dosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I-III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting. METHODS: Advanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs). RESULTS: 588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and -1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(V(d); 0.34). A significant inverse CL-OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07-2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70). CONCLUSIONS: High interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on V(d)). A strong inverse CL-OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored.	bladder
Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells.	BACKGROUND/AIM: Activation of the ubiquitin-proteasome system (UPS) has been shown to be associated with drug resistance in cancer. Using bladder cancer cells, we investigated the association between UPS activation and cisplatin resistance and also the efficacy of UPS-targeting drugs. MATERIALS AND METHODS: We established cisplatin-resistant bladder cancer cells (J82-cisR, T24-cisR) and examined the activation status of the UPS and the efficacy of MLN7243, oprozomib, ixazomib, and RTS-V5. RESULTS: The UPS in cisplatin-resistant bladder cancer cells was activated compared to that in their parental controls. All the UPS-targeting drugs induced apoptosis and inhibited growth more effectively in the cisplatin-resistant bladder cancer cells than they did in the parental controls. Furthermore, these UPS-targeting drugs induced endoplasmic reticulum stress by causing unfolded protein accumulation at lower concentrations in the cisplatin-resistant bladder cancer cells. CONCLUSION: Targeting the UPS could be an effective strategy for treating cisplatin-resistant bladder cancer.	bladder
Evaluation of carbonic anhydrase IX as a potential therapeutic target in urothelial carcinoma.	OBJECTIVE: Carbonic anhydrase IX (CA9) is important in the regulation of intra- and extracellular pH in solid tumors, contributing to cell growth and invasion. In urothelial carcinoma (UC), CA9 has been identified as a urinary marker for disease detection, but its biologic role is unknown. To date, differential gene expression patterns of CA9 in various molecular subtypes and potential effects of CA9 inhibition in UC cells are unknown. We aimed to investigate the function of CA9 and the effects of CA9 inhibition in invasive UC. METHODS: Immunohistochemistry was used to assess CA9 expression in a cohort of 153 patients undergoing radical cystectomy. CA9 expression was correlated with molecular subtype by analysis of the TCGA data and of our own cohort of 223 patients with invasive UC receiving neoadjuvant chemotherapy. CA9 expression was assessed in a panel of 12 UC cell lines by Western Blot and qPCR, and multiple siRNAs were used to silence CA9 in 2 cell lines. Effects of CA9 silencing on cell growth, migration, and invasion were assessed. We also used the small molecule inhibitor U-104 to inhibit CA9 in vitro and in an orthotopic xenograft model. RESULTS: CA9 expression was higher in cancer tissue compared to benign urothelium and was particularly highly expressed in luminal papillary and basal squamous tumors. CA9 expression did not correlate with outcome after neoadjuvant chemotherapy and/or radical cystectomy. Silencing of CA9 by siRNA diminished invasion but did not induce a consistent change of cell growth and migration. Treatment with U-104 led to cell growth reduction only at high concentrations in vitro and failed to have a significant effect on tumor growth in vivo. CONCLUSIONS: The present study confirms over-expression of CA9 in UC and for the first time shows a correlation with molecular subtypes. However, CA9 expression showed no association with the outcome of patients with muscle invasive bladder cancer and inhibition of CA9 did not lead to a consistent inhibition of tumor growth. Based on these data, CA9 exhibits a role neither as a predictive or prognostic marker nor as a therapeutic target in invasive UC.	bladder
The patient-side surgeon plays a key role in facilitating robot-assisted intracorporeal ileal conduit urinary diversion in men.	The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p < 0.001), ileal isolation and anastomosis (73 min vs 45 min, p < 0.001), and stenting (23.0 min vs 6.5 min, p < 0.001). As the experience of the PSS increased, the time of the PSS procedures decreased.	bladder
[Clinicopathologic analysis of 5 cases of urachal adenocarcinoma.].	OBJECTIVES: To summarize the long-term results of patients with urachal carcinoma treated in our center. CLINICAL CASES: The mean age at diagnosis was 48 years. The tumor stage according to Sheldon´s staging was IIB in two, IVA in one and IVB in two cases. Two of the patients underwent radical cystectomy and three underwent a partial one. All of them were urachal carcinomas, three were mucinous, one enteric and the fifth unspecified. All the patients received chemotherapy treatment. The mean follow-up time was 32 months, until death caused by the disease in all five cases. CONCLUSIONS: Despite recent reviews, treatment remains a medical challenge. The importance of surgery is clear, but it is necessary to continue investigate different added treatments.	bladder
High nuclear expression of HIF1α, synergizing with inactivation of LIMD1 and VHL, portray worst prognosis among the bladder cancer patients: association with arsenic prevalence.	PURPOSE: Our study was aimed to understand the importance of LIMD1-VHL-HIF1α pathway in development of bladder carcinoma (BlCa) in association with arsenic prevalence. METHODS: At first, the mRNA expression pattern of the genes of this pathway (LIMD1, VHL and HIF1α) was checked in GEO datasets and in our samples. Next, genetic and epigenetic profiling of LIMD1 and VHL was done in our sample pool, validated in T24 BlCa cell line. The results were next correlated with various clinico-pathological parameters. RESULTS: Differential under-expression of LIMD1 and VHL genes was found in muscle-invasive BlCa (MIBC) in comparison to non-muscle-invasive BlCa (NMIBC). However, HIF1α protein, but mRNA, was found to be overexpressed among the MIBC samples; depicting the probability of HIF1α protein stabilization. Analysis of genetic and epigenetic profiles of LIMD1 and VHL exposed a frequent promoter methylation of LIMD1 gene in MIBC samples. Further, in-depth look into the results unveiled that the high nuclear expression of HIF1α was significantly correlated with genetic alterations of LIMD1, alone or in combination with VHL. Moreover, treating the T24 cells with a de-methylating agent (5-aza-2'-deoxycytidine) re-expressed the methylated LIMD1 and VHL genes, which in turn, reduced the HIF1α protein level significantly. Additionally, patients with high arsenic content (> 112 ng/g, AsH) seemed to have recurrent promoter methylation in LIMD1, as well as co-methylation/alteration of LIMD1 and VHL gene. Lastly, high nuclear expression of HIF1α in association with co-alteration of VHL and LIMD1 showed the worst overall survival (OS) among the patients. CONCLUSION: To conclude, MIBC samples portrayed higher alterations in VHL and LIMD1, thereby, stabilizing HIF1α protein and lowering the OS of patients.	bladder